西维来司钠对大鼠脑缺血/再灌注损伤的保护作用及机制  

Protective effects of sivelestat sodiurm on cerebral ischemia-reperfusion injury in rats and its mechanism

作　　者：丁丽君[1] 董志[1] 乐乐乐[1] 秦黄英[1] 

机构地区：[1]重庆医科大学药学院药理学教研室,重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国药理学通报》2011年第1期54-58,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30572074)

摘　　要：目的探讨西维来司钠对大鼠脑缺血/再灌注损伤的保护作用及机制。方法 90只大鼠随机分成6组,假手术组、I/R组和西维来司钠低、中、高剂量(10、30、90 mg.L-1)组及尼莫地平组。采用改良Zea Longa线栓法制备大鼠局灶性脑缺血(2 h)/再灌注(24 h)损伤模型,西维来司钠各组于再灌注0、3、6 h腹腔注射西维来司钠溶液(sivelestat sodium,SIV,ONO-5046),假手术组和I/R组给予等体积的NS。再灌注24 h,采用改良的Zea Longa评分法对大鼠进行神经行为学评分后,进行缺血脑组织形态学观察及SOD、MDA、MPO活性测定。免疫组化检测缺血脑组织Caspase-3和Caspase-1(ICE)的表达,ELISA法检测缺血侧脑组织匀浆NE的含量。结果西维来司钠可以降低大鼠脑缺血/再灌注损伤的神经功能缺损评分,能不同程度地改善脑组织学损伤,并且升高SOD活性,降低脑组织中MDA、MPO活性,减少脑组织Caspase-3和Caspase-1(ICE)的表达和NE的含量。结论西维来司钠对大鼠脑缺血/再灌注损伤有保护作用,作用机制之一可能与抗炎、抗氧化、抗凋亡有关。Aim To investigate the protective effect of sivelestat sodiurm（SIV） on cerebral ischemia-reperfusion injury in rats and its mechanism.Methods 90 rats were randomly divided into 6 groups：sham operation group,model group and 10,30,90 mg·kg-1 SIV groups,with 15 rats in each group.The model of focal cerebral ischemia-reperfusion in rats was established with modified sutured-occluded method.The rats in SIV groups were injected with SIV at the matched concentration.The rats in sham operation group and model group were injected with saline.And all rats were given more time in 3 hours,6 hours after ischemia.Rats were sacrificed for histologic examination after the behavioral test,and their brains were taken to assay the activities of SOD,MDA,MPO,the content of NE and the expression of Caspase-1（ICE）and Caspase-3.Results SIV at different dosages（10,30,90 mg·kg-1）could obviously decrease neurological deficit score,repair histological injury,and reduce the activities of SOD,MDA and MPO in rats of focal cerebral ischemia-reperfusion injury,and attenuate the expression of Caspase-1（ICE）and Caspase-3.Conclusion SIV can relieve the cerebral ischemia reperfusion injury,and its mechanism may be partly related to its effects of antiinflammation and antioxidation.

关 键 词：西维来司钠 脑缺血/再灌注 保护作用 抗炎 抗氧化 中性粒细胞弹性蛋白酶 Caspase-3 Caspase-1(ICE) 

分 类 号：R-332[医药卫生] R322.81